核黄素代谢病:从机制到临床的系统再认识

孙芳; 杨艳玲; 邵庆亮

doi:10.16689/j.cnki.cn11-9349/r.2026.03.003

PDF(854 KB)

肿瘤代谢与营养电子杂志 ›› 2026, Vol. 13 ›› Issue (3) : 348-353. DOI: 10.16689/j.cnki.cn11-9349/r.2026.03.003

专家论坛

核黄素代谢病:从机制到临床的系统再认识

¹孙芳, ²杨艳玲, ¹邵庆亮

作者信息 +

Riboflavin metabolic disorders: a systematic reassessment from mechanisms to clinical practice

¹Sun Fang, ²Yang Yanling, ¹Shao Qingliang

Author information +

文章历史 +

摘要

核黄素又称维生素B₂,是合成黄素单核苷酸和黄素腺嘌呤二核苷酸的前体,是机体能量代谢与氧化还原平衡的关键调控分子之一,其重要性从传统营养功能拓展到多种疾病的防治。核黄素代谢病包括营养性核黄素缺乏症及遗传性核黄素代谢通路缺陷两大类,涉及核黄素转运、辅酶生成、线粒体递送等多环节缺陷的复杂疾病谱系。本文系统梳理核黄素代谢病的发病机制、遗传缺陷、临床表型、实验室检查、诊断及治疗,以期改进预防和治疗策略,改善患者临床预后。

Abstract

Riboflavin, also known as vitamin B₂,is a synthetic precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). It is one of the key regulatory molecules for energy metabolism and redox balance in the body. The importance of riboflavin has expanded from traditional nutrient functions to the prevention and treatment of multiple diseases. Riboflavin metabolic disorders are classified into nutritional riboflavin deficiency and inherited defects in riboflavin metabolic pathway. The patients manifest a complex spectrum of diseases involving multicomponent defects of riboflavin transport, coenzyme synthesis and mitochondrial delivery. This article systematically reviews the pathogenesis, genetic defects, clinical phenotypes, laboratory examinations, diagnosis and treatment of riboflavin metabolic disorders, aiming to ameliorate the strategies of prevention and treatment, thereby improving clinical prognosis.

导出引用

孙芳, 杨艳玲, 邵庆亮. 核黄素代谢病:从机制到临床的系统再认识[J]. 肿瘤代谢与营养电子杂志. 2026, 13(3): 348-353 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.03.003

Sun Fang, Yang Yanling, Shao Qingliang. Riboflavin metabolic disorders: a systematic reassessment from mechanisms to clinical practice[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2026, 13(3): 348-353 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.03.003

参考文献

[1] MARIOLI C,MUZZI M,COLASUONNO F,et al. Caspase-dependent apoptosis in riboflavin transporter deficiency iPSCs and derived motor neurons[J]. Cell Death Discov,2024,10(1):54.
[2] JIN C,YONEZAWA A. Recent advances in riboflavin transporter RFVT and its genetic disease[J]. Pharmacol Ther,2022,233:108023.
[3] ARAGO M,PIRES L,SANTOS-BUELGA C,et al. Revitalising riboflavin: unveiling its timeless significance in human physiology and health[J]. Foods,2024,13(14):2255.
[4] QIAO Y,CUI Y,TAN Y,et al. Fluoride induces immunotoxicity by regulating riboflavin transport and metabolism partly through IL-17A in the spleen[J]. J Hazard Mater,2024,476:135085.
[5] JAEGER B,HOYTEMA VAN KONIJNENBURG E,GROENVELD M A,et al. Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study[J]. Orphanet J Rare Dis,2024,19(1):410.
[6] O'BRIEN M A,CULICAN S M,SHINAWI M S,et al. Child neurology: five-year update on siblings with riboflavin transporter deficiency: stable visual and neurologic status with continued riboflavin therapy[J]. Neurology,2024,103(11):e209969.
[7] SUBBU K,HILDEBRANDT C,CARACCIO D. Multiple Acyl-coenzyme a dehydrogenase deficiency leading to severe metabolic acidosis in a young adult[J]. AACE Clin Case Rep,2023,9(1):13-16.
[8] MARTINO S,D'ADDABBO P,TURCHIANO A,et al. Deep Intronic ETFDH variants represent a recurrent pathogenic event in multiple Acyl-CoA dehydrogenase deficiency[J]. Int J Mol Sci,2024,25(17):9637.
[9] 周朵, 叶梅玲, 胡真真, 等. 浙江省新生儿多酰基辅酶A脱氢酶缺乏症筛查及随访分析[J]. 浙江大学学报(医学版), 2021, 50(4): 454-462.
[10] SINHA T,IKELLE L,MAKIA M S,et al. Riboflavin deficiency leads to irreversible cellular changes in the RPE and disrupts retinal function through alterations in cellular metabolic homeostasis[J].Redox Biol,2022,54:102375.
[11] ZHANG B,GAO K,CAO J,et al. Maternal riboflavin deficiency causes embryonic defects by activating ER stress-induced hepatocyte apoptosis pathway[J]. Free Radic Biol Med,2024,224:418-435.
[12] ZHANG B,HOU S,TANG J. Riboflavin deficiency and apoptosis: a review[J]. J Nutr,2025,155(1):27-36.
[13] MCNULTY H,PENTIEVA K,WARD M. Causes and clinical sequelae of riboflavin deficiency[J]. Annu Rev Nutr,2023,43:101-122.
[14] 中国妇幼保健协会儿童疾病与保健分会遗传代谢病学组. 多种酰基辅酶A脱氢酶缺乏症的筛查与诊治共识[J]. 中华医学遗传学杂志, 2021,38(5):414-418.
[15] ZOPPI D,RUSSO A,VALLEFUOCO F,et al. Late-onset multiple Acyl-CoA dehydrogenase deficiency (MADD): clinical features, diagnostic challenges, and the role of oxidative stress in pathophysiology[J]. Antioxidants (Basel),2025,14(12):1409.
[16] XU J,LI D,LV J,et al. ETFDH Mutations and flavin adenine dinucleotide homeostasis disturbance are essential for developing riboflavin-responsive multiple Acyl-coenzyme a dehydrogenation deficiency[J]. Ann Neurol,2018,84(5):659-673.
[17] KUO Y C,HSUEH H W,HSUEH S J,et al. A systematic review of late-onset and very-late-onset multiple Acyl-coenzyme a dehydrogenase deficiency: cohort analysis and patient report from Taiwan[J]. Neuromuscul Disord,2021,31(3):218-225.
[18] 中国营养学会医用食品与营养支持分会,中华医学会肠外肠内营养学分会,上海市医学会肠外肠内营养学专科分会,等. 成人肠外营养维生素应用专家共识[J]. 肠外与肠内营养,2024,31(4):193-210.
[20] MOSEGAARD S,BRUUN G H,FLYVBJERG K F,et al. An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple Acyl-CoA dehydrogenation deficiency[J]. Mol Genet Metab,2017,122(4):182-188.
[21] YEE S W,WANG J,GIACOMINI K M. Rare diseases linked to mutations in vitamin transporters expressed in the human blood-brain barrier[J]. Clin Pharmacol Ther,2024,116(6):1513-1520.
[22] BOSCH A M,STROEK K,ABELING N G,et al. The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives[J]. Orphanet J Rare Dis,2012,7:83.
[23] PLANTONE D,PARDINI M,RINALDI G. Riboflavin in neurological diseases: a narrative review[J]. Clin Drug Investig,2021,41(6):513-527.
[24] PENG M Z,SHAO Y X,LI X Z,et al. Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism[J]. Cell Mol Life Sci,2022,79(7):375.
[25] CURTABBI A,GUARÁS A,CABRERA-ALARCÓN J L,et al. Regulation of respiratory complex I assembly by FMN cofactor targeting[J]. Redox Biol,2024,69:103001.
[26] HEDBERG-OLDFORS C,LINDGREN U,VISUTTIJAI K,et al. Lipid storage myopathy associated with sertraline treatment is an acquired mitochondrial disorder with respiratory chain deficiency[J]. Acta Neuropathol,2024,148(1):73.
[27] TAO Z,HUO J,HAO X,et al. Riboflavin in neurological diseases: therapeutic advances, metabolic insights, and emerging genetic strategies[J]. Front Neurol,2025,16:1663136.
[29] ZAMBON A A,GHEZZI D,BALDOLI C,et al. Expanding the spectrum of neonatal-onset AIFM1-associated disorders[J]. Ann Clin Transl Neurol,2023,10(10):1844-1853.
[30] NGUYEN T,LAI H T,FERNANDES R,et al. Apoptosis-inducing factor (AIF) at the crossroad of cell survival and cell death: implications for cancer and mitochondrial diseases[J]. Cell Commun Signal,2025,23(1):264.
[31] GRÜNERT S C,ZIAGAKI A,HEINEN A,et al. Riboflavin 1 transporter deficiency: novel SLC52A1 variants and expansion of the phenotypic spectrum[J]. Genes (Basel),2023,14(7):1408.
[32] 吕拥芬,郭盛. 多种酰基辅酶A脱氢酶缺乏症的发病机制及诊断难点[J]. 中国实用儿科杂志,2024,39(12):901-906.
[33] BROWN K H,HESS S Y,MOORE S E,et al. Neglected micronutrients-considering a broader set of vitamins and minerals in public health nutrition programs worldwide: a narrative review[J]. Am J Clin Nutr,2025,122(3):680-694.
[34] CARREAU C,BENOIT C,AHLE G,et al. Late-onset riboflavin transporter deficiency: a treatable mimic of various motor neuropathy aetiologies[J]. J Neurol Neurosurg Psychiatry,2020:jnnp-2020-323304.
[35] OU Y,WEN Y,CHEN X,et al. A novel ETFDH mutation identified in a patient with riboflavin-responsive multiple Acyl-CoA dehydrogenase deficiency[J]. Intractable Rare Dis Res,2025,14(1):76-80.
[36] ZHANG B,ZHANG D,SUN F,et al. Identification of ETFDH gene c. 487+2 T>A pathogenic variant and mechanisms for polycystic kidney in neonatal onset MADD[J]. Orphanet J Rare Dis,2025,20(1):121.
[37] MEIER C,BURNS K,MANOLIKOS C,et al. Multiple acyl-Coa dehydrogenase deficiency: an underdiagnosed disorder in adults[J]. Intern Med J,2024,54(9):1567-1571.
[38] JAEGER B,LANGEVELD M,BRUNKHORST R,et al. Riboflavin transporter deficiency in young adults unmasked by dietary changes[J]. JIMD Rep,2024,65(4):233-238.
[39] PEA-QUINTANA L,CORRECHER-MEDINA P. Nutritional management of patients with fatty acid oxidation disorders[J]. Nutrients,2024,16(16):2707.
[40] VIGUERA ALTOLAGUIRRE C,STERGACHIS A B,SWEETSER D A,et al. Late-onset multiple Acyl-CoA dehydrogenase deficiency presenting as hyperammonemia and encephalopathy: case series[J]. Neurohospitalist,2025:19418744251324959.